Michael C.V. Jensen, MD
Colleen Annesley, MD
After phase I results of Seattle Children’s Pediatric Leukemia Adoptive Therapy (PLAT-02) trial, published by Gardner et al in Blood,1 showed T-cell immunotherapy to be effective in sending 93% of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) into complete initial remission, researchers have now opened a first-in-human clinical trial aimed at reducing the rate of relapse after the therapy, which is about 50%. The new phase I pilot study, PLAT-03, will examine the feasibility and safety of administering a second T-cell product intended to increase the long-term persistence of the patient’s chimeric antigen receptor (CAR) T cells.
The research team, led by Michael C.V. Jensen, MD, at the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute, is exploring this strategy after discovering that of the patients who relapsed in the PLAT-02 trial, about half of them had lost their CAR T cells. Lasting persistence of the CAR T cells is critical in combating a recurrence of cancer cells.
“While it’s promising that we’re able to get these patients who are very sick back into remission, we’re also seeing that the loss of the CAR T cells in some patients may be opening the door for the cancer to return,” said Colleen Annesley, MD, an oncologist at Seattle Children’s and the lead investigator of the PLAT-03 trial. “We’re pleased now to be able to offer patients who have lost or are at risk of losing their cancer-fighting T cells an option that will hopefully lead to their achieving long-term remission.”
In the PLAT-03 trial, patients will receive “booster” infusions of a second T-cell product, called T antigen-presenting cells (T-APCs). The T-APCs have been genetically modified to express the CD19 target for the CAR T cells to recognize. Patients will receive a full dose of T-APCs every 28 days for at least one—and up to six—doses. By stimulating the CAR T cells with a steady stream of target cells to attack, researchers hope the CAR T cells will reactivate, helping to ensure their persistence long enough to put patients into long-term remission.
PLAT-03 is now open to patients who first enroll in phase II of Seattle Children’s PLAT-02 trial and who are also identified as being at risk for early loss of their reprogrammed CAR T cells or those who lose their reprogrammed CAR T cells within 6 months of receiving them.
“We are pleased to be at a pivotal point where we are now looking at several new strategies to further improve CAR T-cell immunotherapy, so it remains a long-term defense for all of our patients,” said Rebecca Gardner, MD, Seattle Children’s oncologist and the lead investigator of the PLAT-02 trial. “We’re also excited to be working to apply this therapy to several other forms of pediatric cancer beyond ALL, with the hope that T-cell immunotherapy becomes a first line of defense, reducing the need for toxic therapies and minimizing the length of treatment to only weeks.” ■
1. Gardner RA, Finney O, Annesley C, et al: Intent to treat leukemia remission by CD19CAR T cells of defined formulation and dose in children and young adults. Blood. April 13, 2017 (early release online).